hematopoietic system
N |
• mice do not display increased bleeding tendency or thrombitic events over their lifespan
• platelet counts, white cell counts, hematocrits and hemoglobin concentrations are similar to controls
• platelets have normal discoid morphology with normal numbers of alpha- and dense-granules
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• display decreased spreading on immobilized fibrinogen
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• decrease in aggregation rates induced by thrombin (0.025U/ml), collagen (0.8 ug/ml), and TXA2 analog U46619 (0.3 uM)
• higher concentrations of thrombin, collagen, and TXA2 analog U46619 overcome the aggregation defect
• however, ADP-induced aggregation is similar to controls and supplementing with low concentrations of ADP rescues the aggregation defect
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• impaired dense granule secretion when stimulated by thrombin (0.025U/ml), collagen (0.8 ug/ml), and TXA2 analog U46619 (0.3 uM)
• higher concentrations of thrombin, collagen, and TXA2 analog U46619 do not overcome the secretion defect
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homeostasis/metabolism
• display decreased spreading on immobilized fibrinogen
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• decrease in aggregation rates induced by thrombin (0.025U/ml), collagen (0.8 ug/ml), and TXA2 analog U46619 (0.3 uM)
• higher concentrations of thrombin, collagen, and TXA2 analog U46619 overcome the aggregation defect
• however, ADP-induced aggregation is similar to controls and supplementing with low concentrations of ADP rescues the aggregation defect
|
• impaired dense granule secretion when stimulated by thrombin (0.025U/ml), collagen (0.8 ug/ml), and TXA2 analog U46619 (0.3 uM)
• higher concentrations of thrombin, collagen, and TXA2 analog U46619 do not overcome the secretion defect
|
• prolonged time to form a stable thrombosis in an FeCl3-induced mesenteric arteriole thrombosis model
• in an in vitro microfluidic whole-blood perfusion assay thrombi formed are significantly smaller compared to controls
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• prolonged bleeding time in a tail-bleeding assay, with 48% of mice having a bleed time of over 15 minutes compared to 19% of wild-type controls
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